The present invention relates to ultrasonic imaging and therapy apparatus and method incorporating both ultrasonic observation and therapeutic waves, and more specifically to apparatus and method designed to allow real time, noise-free imaging of a treatment site to which high intensity focused ultrasound is directed.
Ultrasound has gained acceptance as an imaging technique particularly well suited to providing information about a patient""s internal structures without risk of exposure to potentially harmful radiation, as may occur when using X-ray imaging techniques. The first recorded use of ultrasound as an imaging technique was by Dr. Karl Dussik, a Psychiatrist at the hospital in Bad Ischl, Austria; who tried to locate brain tumors using ultrasound. He used two opposed probes, including one that transmitted ultrasound waves, while the other probe received them. With these probes, he transmitted an ultrasound beam through a patient""s skull, and used the received signal to visualize the cerebral structure by measuring the ultrasound beam attenuation. He published his technique in 1942, in an article entitled, xe2x80x9cHyperphonography of the Brain.xe2x80x9d
Specially manufactured medical diagnostic equipment using ultrasound became available in the 1950""s. An ultrasound examination is a safe diagnostic procedure that uses very high-frequency sound waves to produce an image of the internal structures of the body. Many studies have shown that these sound waves are harmless and may be used with complete safety, even on pregnant women, where the use of X-rays would be inappropriate. Furthermore, ultrasound examinations are sometimes quicker and typically less expensive than other imaging techniques.
More recently, the use of high intensity focused ultrasound (HIFU) for therapeutic purposes, as opposed to imaging, has received significant attention in the medical community. HIFU therapy employs ultrasound transducers that are capable of delivering 1,000-10,000 W/cm2 at a focal spot, in contrast to diagnostic ultrasound where intensity levels are usually below 0.1 W/cm2. A portion of the mechanical energy from these high intensity sound waves is transferred to the targeted location as thermal energy. The amount of thermal energy thus transferred can be sufficiently intense to cauterize tissue, or to cause tissue necrosis (by inducing a temperature rise to beyond 70xc2x0 C.) without actual physical charring of the tissue. Tissue necrosis can also be achieved by mechanical action alone (i.e., by cavitation that results in mechanical disruption of the tissue structure). Further, where the vascular system supplying blood to an internal structure is targeted, HIFU can be used to induce hemostasis. The focal point of this energy transfer can be tightly controlled so as to obtain tissue necrosis in a small target area without damaging adjoining tissue. Thus, deep-seated tumors can be destroyed with HIFU without surgical exposure of the tumor site.
A particular advantage of HIFU therapy over certain traditional therapies is that HIFU is less invasive. The current direction of medical therapy is progressively toward utilizing less-invasive and non-operative approaches, as will be evident from the increasing use of laparoscopic and endoscopic techniques. Advantages include reduced blood loss, reduced risk of infection, shorter hospital stays, and lower health care costs. HIFU has the potential to provide an additional treatment methodology consistent with this trend by offering a method of non-invasive surgery. HIFU enables transcutaneous tumor treatment without making a single incision, thus avoiding blood loss and the risk of infection. Also, HIFU therapy may be performed without the need for anesthesia, thereby reducing surgical complications and cost. Most importantly, these treatments may be performed on an outpatient basis, further reducing health care cost, while increasing patient comfort.
The use of HIFU for the destruction of tumors is a relatively new technique. The first clinical trials were performed on patients with hyperkinetic and hypertonic disorders (symptoms of Parkinson""s disease). HIFU was used to produce coagulation necrosis lesions in specific complexes of the brain. While the treatment was quite successful, monitoring and guidance of the HIFU lesion formation was not easily achieved (N. T. Sanghvi and R. H. Hawes, xe2x80x9cHigh-intensity focused ultrasound,xe2x80x9d Gastrointestinal Endoscopy Clinics of North America, vol. 4, pp. 383-95, 1994). The problem has been that the high energy therapeutic wave introduces a significant amount of noise into an ultrasound imaging signal employed to monitor the treatment site, making simultaneous imaging and treatment difficult. Indeed, the high energy of the HIFU can completely overwhelm conventional ultrasonic imaging systems. However, the advancement of imaging modalities has provided grounds for renewed research and development of HIFU-based tumor treatment methods. In general, current methods involve the use of discrete imaging and therapeutic steps, i.e., a treatment site is first imaged, therapy is applied, and the treatment site is again imaged. The therapeutic transducer is de-energized during the imaging process to eliminate the noise it would otherwise produce. However, the time required for carrying out each of these discrete steps has prevented the significant potential of HIFU from being fully realized, since real-time guidance and monitoring of HIFU has not been achieved.
Two HIFU-based systems have been developed for the treatment of benign prostatic hyperplasia (BPH) in humans (E. D. Mulligan, T. H. Lynch, D. Mulvin, D. Greene, J. M. Smith, and J. M. Fitzpatrick, xe2x80x9cHigh-intensity focused ultrasound in the treatment of benign prostatic hyperplasia,xe2x80x9d Br J Urol, vol.70, pp.177-80, 1997). These systems are currently in clinical use in Europe and Japan, and are undergoing clinical trials in the United States. Both systems use a transrectal HIFU probe to deliver 1,000-2,000 W/cm2 to the prostate tissue through the rectum wall. No evidence of damage to the rectal wall has been observed during a rectoscopy, performed immediately after HIFU treatment (S. Madersbacher, C. Kratzik, M. Susani, and M. Marberger, xe2x80x9cTissue ablation in benign prostatic hyperplasia with high intensity focused ultrasound,xe2x80x9d Journal of Urology, vol. 152, pp. 1956-60; discussion 1960-1, 1994). Follow-up studies have shown decreased symptoms of BPH (i.e., increased urinary flow rate, decreased post-void residual volume, and decreased symptoms of irritation and obstruction; see S. Madersbacher, C. Kratzik, N. Szabo, M. Susani, L. Vingers, and M. Marberger, xe2x80x9cTissue ablation in benign prostatic hyperplasia with high-intensity focused ultrasound,xe2x80x9d European Urology, vol. 23 Suppl 1, pp. 39-43, 1993). In this prior art use of HIFU, ultrasound imaging is employed to obtain pre- and post-treatment maps of the prostate and the treatment area. Significantly, the noise induced in the imaging signal by the HIFU prevents real time imaging of the treatment site. Therefore, strict imaging requirements, such as no patient movement during the entire procedure (thus, the need for general or spinal anesthesia), limit the performance of these systems. It should be noted that respiration alone can result in sufficient patient movement so that the HIFU is no longer targeted as precisely as would be desired. Especially where the treatment site is adjacent to critical internal structures that can be damaged, the lack of real time imaging is a significant drawback to an otherwise potentially very useful treatment methodology.
HIFU has also been studied for the de-bulking of malignant tumors (C. R. Hill and G. R. ter Haar, xe2x80x9cReview article: high intensity focused ultrasoundxe2x80x94potential for cancer treatment,xe2x80x9d Br J Radiol, vol. 68, pp. 1296-1303, 1995). Prostate cancer (S. Madersbacher, M. Pedevilla, L. Vingers, M. Susani, and M. Marberger, xe2x80x9cEffect of high-intensity focused ultrasound on human prostate cancer in vivo,xe2x80x9d Cancer Research, vol.55, pp.3346-51, 1995) and testicular cancer (S. Madersbacher, C. Kratzik, M. Susani, M. Pedevilla, and M. Marberger, xe2x80x9cTranscutaneous high-intensity focused ultrasound and irradiation: an organ-preserving treatment of cancer in a solitary testis,xe2x80x9d European Urology, vol. 33, pp. 195-201, 1998) are among the cancers currently being investigated clinically for potential treatment with HIFU. An extensive clinical study to extracorporeally treat a variety of stage 4 cancers is underway in England (A. G. Visioli, I. H. Rivens, G. R. ter Haar, A. Horwich, R. A. Huddart, E. Moskovic, A. Padhani, and J. Glees, xe2x80x9cPreliminary results of a phase I dose escalation clinical trial using focused ultrasound in the treatment of localized tumors,xe2x80x9d Eur J Ultrasound, vol.9, pp. 11-8, 1999). The cancers involved include prostate, liver, kidney, hipbone, ovarian, breast adenoma, and ocular adenoma. No adverse effects, except one case of skin bum have been observed. Significantly, none of these studies has addressed the noise issue preventing the real time imaging of HIFU treatment.
U.S. Pat. No. 5,471,988 teaches the combination of a HIFU therapy transducer and an imaging transducer on the same probe. This patent points out that one of the problems with the prior art has been obtaining scanning data in conjunction with the therapeutic operation of the probe, due to the noise that the therapeutic wave introduces into the imaging signal. The reference notes that a problem with non-simultaneous imaging is that in the time frame between when the image was last seen, and when the therapy transducer is energized, it is possible that the probe will move relative to a target area. Thus, the therapeutic energy may be applied to an area that is not the desired target. The patent teaches that it is desirable for the therapy and imaging transducers operate at different frequencies, e.g., 12 MHz for the imaging transducer and less than 2 MHz for the therapeutic transducer. It is also suggested that incorporating noise reduction circuitry in the imaging system can help to reduce the impact of the interfering noise. Unfortunately, it has been determined that this approach does not work as effectively as would be desired.
U.S. Pat. No. 5,769,790 describes another combination probe that includes transducers for both ultrasonic imaging and treatment. This patent teaches that prior to the delivery of therapy, verification of the focal point of the therapeutic wave is needed and advocates energizing the therapy transducer at a relatively low power level and using the imaging transducer to detect the low power ultrasound waves produced by the therapy transducer that are reflected from the target site. This technique provides a B-mode image where the only area in the image to be significantly illuminated is the focus of the therapy transducer. The image frame can then be interleaved with or super imposed on a normal B-mode image frame where both transmit and receive functions are performed using the imaging transducer. Once the focal point of the therapy transducer has been verified in this manner, therapy can be delivered by applying higher power, longer duration excitation to the therapy transducer. Significantly, the ""790 patent does not teach the simultaneous scanning of the treatment area with the ultrasonic signal transmitted by the imaging transducer while the therapy transducer is operational, nor does the ""790 patent discuss how the noise problem can be addressed.
U.S. Pat. No. 5,895,356 is directed to a method and apparatus optimized for the treatment of diseases of the prostate. This reference teaches that the echogenicity of tissue heated to over 60xc2x0 C. changes so that when imaged using an ultrasonic imaging transducer, a bright spot appears in the viewing field, and that this echogenicity is transient (it fades with time). The patent also teaches storing the location of this region of higher echogenicity in a memory of an imaging system and superimposing the known focal point of the therapeutic transducer on the display of the imaging system, so that the therapeutic transducer can be focused on an area of interest prior to energizing the therapeutic transducer. The patent teaches imaging using low power ultrasound, focusing using the known focal point, ceasing the imaging, applying a higher power ultrasound therapy, ceasing the therapy, and then using low power ultrasound to generate an image of the area just treated. Significantly, the patent does not discuss how noise produced by the simultaneous operation of imaging and therapeutic ultrasound can be reduced.
While the prior art has recognizes the advantages that real time imaging can provide, a suitable method of achieving such imaging has not been described. It would be desirable to provide a method in which simultaneous imaging and therapy can be achieved in real time without a noise signal degrading the image quality of the treatment site.
Furthermore, there are many medical conditions that could benefit from simultaneous treatment and imaging using HIFU. In particular, it appears that the treatment of gynecological and obstetrical disorders could be significantly enhanced. For example, uterine fibroids, which are benign tumors of the uterus and are found in more than half of all women, could be treated using an image-guided HIFU therapy system. Approximately 30% of all hysterectomies are related to these uterine fibroids. Current treatment methods for uterine fibroids include both drug therapy and surgery. Drug therapy has virtually a 100% rate of tumor reoccurrence once the drug therapy has stopped, and the drug therapy itself includes numerous negative side effects. The rate of reoccurrence is significantly less (about 15%) for the surgical therapy, though the surgical procedure is invasive, requiring a significant recovery period, and involves significant risks, such as blood loss, damage to related organs, and the ever present risk of infection. It is estimated that uterine fibroid procedures in the United States alone account for 1.2 to 3.6 billion dollars in annual medical costs.
Thus, it would be desirable to develop simultaneous or real time imaging and therapeutic ultrasound methods and apparatus. Initially, such methods and apparatus might be optimized for the treatment of uterine fibroids, and other gynecological and obstetrical disorders. Such treatment is expected to compare favorably with the costs for the current drug related therapy for the treatment of uterine fibroids and should compare favorably with the higher success rate of the current surgical procedures, but without the attendant risks.
In accord with the present invention, a method is defined for using ultrasound to simultaneously image a target area and to provide therapy to a treatment site within the target area in real time. The method employs a scanning ultrasonic transducer system adapted to scan a target area and to provide imaging data for the target area, a processor adapted to manipulate the imaging data, a display capable of providing a visual representation of the imaging data to a user to produce a displayed target area, and a therapeutic ultrasonic transducer system adapted to provide pulsed waves of HIFU to the treatment site within the target area.
The method includes the steps of scanning the target area to generate the imaging data, and displaying a visual representation of the imaging data. A treatment site is selected from within the displayed target area; and the therapeutic ultrasonic transducer system is energized to produce the therapeutic waves. Synchronization of the therapeutic ultrasonic transducer system relative to the scanning ultrasonic transducer system is adjusted such that any noise within the imaging data arising from the therapeutic waves is shifted away from the image of the treatment site. Thus, a noise-free image of the treatment site is provided.
In one embodiment, the therapeutic ultrasonic transducer system is initially energized at a level that is not energetic enough to produce a therapeutic effect at the treatment site, but is sufficiently energetic to produce a change in the echogenicity of tissue at the treatment site. This change in echogenicity is detected by the scanning ultrasonic transducer system, so that the focal point of the therapeutic ultrasonic transducer system is clearly displayed, enabling the therapeutic ultrasonic transducer system to be focused at a desire position for the treatment site. Once properly focused, the energy level of the pulsed therapeutic wave is increased to a therapeutic level that is sufficiently energetic to produce a desired therapeutic effect.
In addition to monitoring for changes in the treatment site, the rest of the target area can be monitored to detect any changes to any non-treatment site area due to the HIFU. Such a change is undesirable, and when noticed, the therapeutic ultrasonic transducer system can be de-energized to prevent further changes to non-treatment site areas, even if the desired therapeutic effect has not yet been achieved at the treatment site.
Preferably, the processor is capable of manipulating the imaging data by effecting scan conversion processing, color flow processing, Doppler processing, B-mode processing or M-mode processing. In one embodiment, the three-dimensional (3D) location of the previously treated sites are stored and appear on the display.
In one preferred embodiment, the target area is the reproductive system of a mammalian female, and the desired therapeutic effect is applied to a uterine fibroid, an endometrial polyp, a follicular cyst, a polycystic ovary, a dermoid cyst, a corpus luteum cyst, an ectopic pregnancy, a cornual pregnancy, a multifetal pregnancy, a uterine malformation, an endometrial hyperplasia, an adenomyosis condition, and endometriosis condition, or an excessive bleeding condition. The treatment of disorders of the female reproductive system using the method of the present invention can be achieved by positioning the scanning ultrasonic transducer system and the therapeutic ultrasonic transducer system adjacent to the female reproductive system. Vaginal, rectal, abdominal, and laparoscopic approaches are contemplated. Accordingly, probes adapted for use in the vaginal canal and the rectum are also defined. Preferably, these probes incorporate both the scanning ultrasonic transducer system and the therapeutic ultrasonic transducer system. The methods include the step of inserting the probe into the appropriate cavity, and advancing the probe until the probe is adjacent to a target area before energizing the scanning ultrasonic transducer system. The focal point of the HIFU is positioned on the pathologic tissue.
In further embodiments using the above-described probes, the step of energizing the therapeutic ultrasonic transducer system generates frequencies within the range of 0.5 MHz to 10 MHz. An even more preferred range for the therapeutic ultrasonic transducer system is 1 MHz to 3.5 MHz.
In one embodiment, the therapeutic ultrasonic transducer system includes a phased array that enables the focal point of the therapeutic ultrasonic transducer system to be effectively enlarged. In another embodiment, the therapeutic ultrasonic transducer system comprises a vibrating element that is energized to cause a focal point of the therapeutic ultrasonic transducer system to be varied. The step of energizing the vibrating element causes the therapeutic ultrasonic transducer system to vibrate with a frequency in the range of 1 to 5 Hz, thereby avoiding the heating of tissue not associated with the treatment site in the unfocused regions of the HIFU beam. Alternately, the vibrating element causes the therapeutic ultrasonic transducer system to vibrate with a frequency in the range of 10 to 50 Hz, thereby increasing an amount of energy applied to the treatment site, while avoiding undesired cavitational effects.
The method enables HIFU to be used to cause the cauterization of tissue at the treatment site for arresting bleeding, preventing bleeding, or causing tissue necrosis. The HIFU can also be used to cause the necrosis of tissue at the treatment site by cavitation or thermal effects, or to ablate tissue at the treatment site.
Another aspect of the present invention is a method for treating a tumorous growth by damaging only selected regions within the tumorous growth. The steps of the method involve using the scanning ultrasonic transducer system to produce an image of the target area on the display as a visual representation of the target area. A selected region from within the tumorous growth is then selected as a treatment site.
The therapeutic ultrasonic transducer system is focused on the selected region until the desired level of damage is obtained. A different region within the tumorous growth is selected; and the steps are repeated until a desired pattern of damaged areas has been formed in the tumorous growth. After waiting a period of time sufficient to allow the macrophagic processes to remove necrotic tissue from the damaged areas, the treatment is repeated, until the tumorous growth is substantially destroyed.
Another aspect of the present invention is directed to a system for simultaneously imaging and applying treatment using ultrasound. The system includes elements that carryout functions generally corresponding to the steps of the methods discussed above.